Double whammy
In collaboration with Ghent University, Labo
Smeets has developed a new technology
that enables the continuous production of water-soluble
granules. Managing director
Jef Verplaetse explains how twin screw extruders
can improve the bioavailability
of medicines that are not easily soluble in water.
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The advantages of the
Twin Screw Granulator are a continuous process,
limited upscaling problems and the absence
of solvents.
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Poorly soluble drugs present a challenge: no
matter
how potent the active ingredient, there are
problems of incomplete absorption and low
bioavailability. The recipients are thus unlikely
to benefit
from the full clinical effect. This is particularly
the case for
medicines belonging to class II (poorly soluble,
highly
permeable) and class IV (poorly soluble, poorly
permeable)
of the biological classification system. Where
such drugs
are administered via drinking water, only a small
proportion of the active ingredient is released:
tests have
shown figures as low as 15%.
| "The
technology ensures a very
intense and effective blending
under strictly controllable
conditions, which helps ensure
the stability of APIs." |
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In response to this situation, Labo Smeets has
pioneered
its latest technology. In collaboration with Ghent
University, the Belgian pharmaceutical powders
company
has developed a granulation technique for converting
poorly soluble drugs into highly soluble granules.
“If a drug is to be administered via drinking
water,
dissolving it is key,” says managing director
Jef Verplaetse.
“Our granules guarantee dissolution of 100%.”
The benefits are obvious: high solubility leads
to
a swift release of the active pharmaceutical ingredient
(API), which in turn increases bioavailability.
This
minimises wastage, because less API is needed
to
produce the same effect.
Twin-screw technology
Although the Twin Screw Granulator used for this
purpose
did not become operational until January 2011,
the
technology was first envisioned decades ago.
“The concept of using twin screw extruders
for the
granulation of drug preparations started in the
mid-1980s,”
says Verplaetse. “However, granules were
not
homogeneous and required a great deal of optimisation.”
A drug load of up to 60% can be achieved for drugs
of
class II and class IV of the BCS system.
The technology now ensures a very intense and
effective blending under strictly controllable
conditions, which helps ensure the stability of
APIs. Moreover, the continuous granulation process,
as distinct from batch production, is speedy and
straightforward. “The main problem of batch
production is the scale-up from laboratory to
industrial production capacity,” explains
Verplaetse. “Such problems can be avoided
with a continuous granulation technology, in which
the only parameter that needs to be changed is
production time.” Finally, the low temperatures
at which the blending process occurs offers interesting
perspectives for temperature-sensitive APIs.
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Why use a twin screw
extruder?
The pharmaceutical industry
is becoming ever more interested in continuous
process technologies. Such technologies
present many benefits, not least the fact
they enable a larger production capacity,
reduce time and costs, and avoid scale-up
problems.
Twin screw extruders have been used for
continuous
production processes for many years. Particularly
prominent in the plastics industry, in which
polymers
are mixed with additives to give plastic
compounds,
they facilitate a very intense and effective
blending
under strictly controllable temperature
conditions
Generally, twin screw extruders are preferred
to
single screw extruders because they give
better mixing
at lower melt temperatures, and benefit
from greater
flexibility in terms of their design.
Despite the long pedigree of this technology,
only
now is the pharmaceutical industry starting
to reap
its benefits. With recent developments focusing
on
the optimisation of the screw profiles and
the choice
of materials used, twin screw extruders
may now
be used for producing homogeneous granules
for
drug preparations.
The Twin Screw Granulator (Pharma TSG 24)
used
by Labo Smeets is supplied by Thermo Scientific,
an
important player in the production of twin
screw
granulators and extruders. It has been operational
since January 2011 and, in its production
of water
soluble granules, has been put to the most
pioneering
of purposes.
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Solubility needs
At present, Labo Smeets’ focus is the veterinary
market. While mixing drugs with animal feed is
arguably simpler than dissolving them in water,
it is difficult to control the concentration level
in feed granules or to estimate batch sizes with
any accuracy. Highly soluble drugs are therefore
a pressing need. Applications in the human drugs
market may also be on their way. Labo Smeets has,
for example, successfully developed a paracetamol
suitable both for animals and people.
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"The
new patented technology
offers new opportunities for the
lifecycle management of drugs." |
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“Bioavailability is going to become ever
more important for
human medicines,” says Verplaetse. “APIs
that are taken orally
should be available for the body and not simply
wasted.
Improved bioavailability also means that the effect
of the drug
as a function of the given doses can be better
understood.”
New horizons
Twin screw granulation has many possible applications,
which are yet to be explored. While Labo Smeets
has
concentrated mainly on melt granulation with a
hydrophilic matrix, the same technology can be
used with
a lipophilic matrix. This should bode especially
well for the
manufacture of tablets.
“Another field we are looking into is wet
granulation,” says
Verplaetse. “The excellent blending properties
of the twin screw
extruders can make a high-quality granulate. Finally,
we are
considering polymer granulation applications for
controlled
release, using ethyl cellulose or polyethylene
oxides as carriers.”
The new patented technology offers new opportunities
for
the lifecycle management of drugs. The major advantage
of
the technology is that, as well as improving solubility
and
bioavailability, it enables the creation of new
lifecycle
opportunities for old molecules. In a time when
patents are
expiring, new creative ideas are needed to ensure
the
continued value of those products: Labo Smeets’
twin screw
granulation process is one such innovation.
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Company profile
Laboratoria Smeets
For further information, visit: www.labosmeets.be
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